低肌肉生长抑制素（myostatin）和高MUC1水平与哮喘患者对美泊利单抗和奥马珠单抗更好的反应相关：蛋白质-蛋白质相
2023/12/20
低肌肉生长抑制素（myostatin）和高MUC1水平与哮喘患者对美泊利单抗和奥马珠单抗更好的反应相关：蛋白质-蛋白质相互作用分析
摘要引言：随着生物制剂的不断增多，需要生物标志物来指导哮喘患者选择生物制剂治疗。我们的目标是识别与奥马珠单抗和美泊利单抗反应相关的蛋白质。
方法：使用基于适配体的蛋白质组学分析（SomaScan）对接受奥马珠单抗（n = 29）或美泊利单抗（n = 22）治疗的51名中重症哮喘患者的1437种蛋白质进行评估。反应定义为治疗启动后12个月内哮喘相关发作的变化。所有模型均根据年龄、性别和治疗前恶化率进行调整。此外，体质指数包括在奥马利兹单抗模型中，嗜酸性粒细胞计数包括在美泊利单抗模型中。我们使用负二项回归分析以校正虚发现率（FDR）并进行基因集富集分析（GSEA）以识别相关通路，评估分子特征与反应之间的关联。
结果：超过三分之二的患者为女性。奥马珠单抗患者的平均年龄为42岁，美泊利单抗患者的平均年龄为57岁。在基线时，奥马珠单抗的平均恶化率为每年1.5次，美泊利单抗为每年2.4次。美泊利单抗反应更好与LOXL2水平降低（未经校正p：1.93 × 10E-05，经FDR校正：0.028）和myostatin水平降低（未经校正：3.87 × 10E-05，经FDR校正：0.028）相关。奥马珠单抗反应更好与CD9抗原水平升高（未经校正：5.30 × 10E-07，经FDR校正：0.0006）和MUC1水平升高（未经校正：1.15 × 10E-06，经FDR校正：0.0006）相关，而与LTB4R水平降低（未经校正：1.12 × 10E-06，经FDR校正：0.0006）相关。蛋白质-蛋白质相互作用网络建模显示，在接受美泊利单抗治疗的患者中，TNF和NF-kB信号通路丰富，而在接受奥马珠单抗治疗的患者中，涉及MAPK的多个通路，包括FcER1通路。
结论：该研究为与重症哮喘患者对美泊利单抗或奥马珠单抗反应相关的蛋白质提供了新的基础数据，并需要进一步验证作为治疗选择的潜在生物标志物。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Respir Res. 2023 Dec 6;24(1):305. doi: 10.1186/s12931-023-02620-1.)
(Respir Res. 2023 Dec 6;24(1):305. doi: 10.1186/s12931-023-02620-1.)
Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein-protein interaction analyses
Ayobami Akenroye, Tanawin Nopsopon, Laura Cho, Matthew Moll, Scott T Weiss
Abstract
Introduction: Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab.
Methods: Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways.
Results: Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E-05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E-05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E-07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E-06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E-06, FDR-corrected: 0.0006) with worse response. Protein-protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab.
Conclusions: This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection.
上一篇：
重症嗜酸性粒细胞性哮喘患者贝那利珠单抗治疗中每日维持吸入糖皮质激素减量研究：一项随机多中心开放标签4期临床试验
下一篇：
Tezepelumab可降低气道上皮细胞IL-33和T2炎症，以应对哮喘患者的病毒刺激
